CONTRIBUTION OF DONOR-SPECIFIC ANTIBODIES TO ACUTE ALLOGRAFT-REJECTION - EVIDENCE FROM B-CELL-DEFICIENT MICE

Background. The role of T lymphocytes in acute allograft rejection is well established. The involvement of B lymphocytes in this process, ho wever, is more controversial. A series of reports showed that mice wit hout a functional B-cell compartment rejected allografts with the same kinetics as control animals. In rats, however, alloantibodies were fo und to play a decisive role in allograft rejection. To provide an expl anation for the discrepant results, we readdressed the role of B cells and antibodies in mice with disrupted immunoglobulin mu chain genes, The use of cyclosporine (CsA), which strongly suppresses T cells, allo wed us to focus specifically on the function of B cells, Methods, C57B L/6 mice rendered B cell deficient by targeted disruption of the immun oglobulin mu chain gene (referred to as mu MT/mu MT mice) and mu MT/control mice with one functional mu chain were heterotopically transpl anted with fully MHC-disparate BALB/c hearts, CsA was administered sub cutaneously by Alzet osmotic pumps. Normal and immune serum specific f or donor hearts was given to assess the role of antibodies in the reje ction process, Results, Both B cell-deficient mu MT/mu MT and heterozy gous mu MT/+ mice were found to reject transplanted hearts within a si milar period of time. In contrast, when T cells were partially suppres sed with CsA, graft survival was significantly prolonged in mu MT/mu M T mice as compared with heterozygous controls, Passive transfer of don or-specific immune serum, obtained from mu MT/+ animals rejecting allo geneic hearts, to CsA-treated mu MT/mu MT mice significantly accelerat ed allograft rejection as opposed to recipients treated with normal se rum, Conclusions. B lymphocytes and antibodies play an important role in acute allograft rejection particularly when the dominant T-cell com partment is partially suppressed.